On October 22, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it results from the phase III ALESIA study, showing that Alecensa (alectinib) met its primary endpoint of investigator-assessed (INV) progression-free survival (PFS) (Press release, Hoffmann-La Roche, OCT 22, 2018, View Source [SID1234530314]). Alecensa significantly reduced the risk of disease worsening or death by 78%, compared to crizotinib, when given as an initial (first-line) monotherapy treatment in Asian patients with anaplastic lymphoma kinase (ALK)-positive advanced or metastatic non-small cell lung cancer (NSCLC) (hazard ratio [HR]=0.22, 95% CI: 0.13-0.38).[1] Median PFS reported by the investigators was not yet reached in patients who received Alecensa (95% CI: 20.3 months-not reached) versus 11.1 months (95% CI: 9.1-13.0 months) in those who received crizotinib.[1] The safety profile of Alecensa was consistent with that observed in previous studies.[1]

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"The ALESIA study supports the use of Alecensa as the standard of care for newly diagnosed advanced or metastatic ALK-positive lung cancer across multiple populations," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "Alecensa has received rapid regulatory approvals for first-line treatment in 65 countries to date, including in China."

Median PFS reported by an independent review committee (IRC), a secondary endpoint, was not yet reached in patients who received Alecensa (95% CI: 16.7 months-not reached), versus 10.7 months (95% CI: 7.4 months-not reached) in patients who received crizotinib (HR=0.37, 95% CI: 0.22-0.61).[1] The phase III ALESIA study also demonstrated that compared to crizotinib, Alecensa reduced the risk of disease progression in the central nervous system (CNS), another secondary endpoint in the study, by 86% (HR=0.14, 95% CI: 0.06-0.30).[1]

The ALESIA data are being officially presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress during a Presidential Symposium on 22 October at 16:30 (Abstract LBA10 Presidential Symposium).[3]

This is the third phase III study to show that Alecensa as a first-line treatment significantly reduced the risk of disease worsening or death (PFS) compared to crizotinib in patients with ALK-positive advanced or metastatic NSCLC.[2;3;4] The results reinforce the findings of the phase III global ALEX study, which found that Alecensa significantly reduced the risk of disease progression or death (PFS) by 57% (HR=0.43, 95% CI: 0.32-0.58) compared to crizotinib after two years of follow-up in people with ALK-positive metastatic NSCLC, as assessed by the investigator.[3] The ALEX study also showed that Alecensa more than tripled median PFS to nearly three years (34.8 months, 95% CI: 17.7 months-NE) compared to crizotinib (10.9 months, 95% CI: 9.1-12.9 months) and demonstrated superior efficacy compared to crizotinib regardless of the presence of CNS metastases at baseline, a secondary endpoint.[3] INV median PFS for people without CNS metastases at baseline was 34.8 months with Alecensa (95% CI: 22.4 months-NE) versus 14.7 months (95% CI: 10.8-20.3 months) with crizotinib (HR=0.47, 95% CI: 0.32-0.71).[3] INV median PFS for people with CNS metastases at baseline was 27.7 months in the Alecensa arm (95% CI: 9.2 months-NE) versus 7.4 months (95% CI: 6.6-9.6 months) in the crizotinib arm (HR=0.35, 95% CI: 0.22-0.56).[3]

The ALESIA study was a bridging study, designed to show consistency with the phase III ALEX study and was not powered to show superiority vs crizotinib. It completes a post-approval agreement with the National Drug Administration of China (CNDA) to demonstrate consistency between the ALESIA and ALEX studies, following the priority review and rapid approval of Alecensa in August this year.[5] The regulatory approval in China is one of the latest of 65 countries for the use of Alecensa as a first-line monotherapy for people with ALK-positive NSCLC.[6]

About the ALESIA study[7]
ALESIA (NCT02838420) is a randomised, multicentre, open-label phase III study evaluating the efficacy and safety of Alecensa versus crizotinib, and the pharmacokinetics of Alecensa in Asian patients with treatment-naive ALK-positive advanced or metastatic NSCLC. Patients were randomised (2:1) to receive either Alecensa or crizotinib. The primary endpoint of the ALESIA study is PFS as assessed by the investigator using the RECIST v1.1 criteria. Secondary endpoints include: PFS, time to CNS progression and CNS ORR assessed by IRC, objective response rate and duration of response assessed by the investigator, overall survival, health-related quality of life and safety. The multicentre study was conducted in 187 patients across 21 sites in three countries.

About Alecensa
Alecensa (RG7853/AF-802/RO5424802/CH5424802) is a highly selective, CNS active, oral medicine created at Chugai Kamakura Research Laboratories and is being developed for people with NSCLC whose tumours are identified as ALK-positive.[6] ALK-positive NSCLC is often found in younger people who have a light or non-smoking history.[8] It is almost always found in people with a specific type of NSCLC called adenocarcinoma.[8] Alecensa is now approved in 65 countries as an initial (first-line) treatment for ALK-positive, metastatic NSCLC, including in the US, Europe, Japan and China.[6]

On October 22, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported positive results from the Phase III IMpower130 study of Tecentriq (atezolizumab) plus chemotherapy (carboplatin and Abraxane [albumin-bound paclitaxel; nab-paclitaxel]) for the initial (first-line) treatment of people with previously untreated metastatic non-squamous non-small cell lung cancer (NSCLC) (Press release, Hoffmann-La Roche, OCT 22, 2018, View Source [SID1234530310]). The analysis showed that Tecentriq plus chemotherapy helped people live significantly longer compared to chemotherapy alone (median overall survival [OS] =18.6 versus 13.9 months; hazard ratio [HR]=0.79; 95% CI: 0.64–0.98; p=0.033) in the intention-to-treat wild-type (ITT-WT) population.[1] The Tecentriq-based combination also significantly reduced the risk of disease worsening or death (progression-free survival; PFS) compared to chemotherapy alone (median PFS=7.0 versus 5.5 months; HR=0.64; 95% CI: 0.54–0.77; p<0.0001) in the ITT- WT population.1 Safety for the Tecentriq plus chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination.

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"Initial treatment with this Tecentriq-based combination provided a significant survival benefit for people with non-squamous non-small cell lung cancer, the most common form of lung cancer," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "Lung cancer is a complex disease and this combination could offer a new potential treatment option. We will work with global health authorities to bring this regimen to people living with this disease as soon as possible."

The data will be presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress on 22 October 2018, 09:15–09:30 am; Hall A1 – Room 17 (Abstract LBA53).

About the IMpower130 study
IMpower130 is a Phase III, multicentre, open-label, randomised study evaluating the efficacy and safety of Tecentriq in combination with carboplatin and nab-paclitaxel versus chemotherapy (carboplatin and nab-paclitaxel) alone for chemotherapy-naïve patients with stage IV non-squamous NSCLC. The study enrolled 723 people who were randomised (2:1) to receive:

Tecentriq plus carboplatin and nab-paclitaxel (Arm A), or
Carboplatin and nab-paclitaxel (Arm B, control arm)
During the treatment-induction phase, people in Arm A received Tecentriq and carboplatin on day 1 of each 21-day cycle, and nab-paclitaxel on days 1, 8 and 15 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit, whichever occurs first. People received Tecentriq during the maintenance treatment phase until loss of clinical benefit was observed.

During the treatment-induction phase, people in Arm B received carboplatin on day 1 and nab-paclitaxel on days 1, 8 and 15 of each 21-day cycle for 4 or 6 cycles or until disease progression, whichever occurs first. People received best supportive care during the maintenance treatment phase. Switch maintenance to pemetrexed was also permitted. People who were consented prior to a protocol revision were given the option to crossover to receive Tecentriq as monotherapy until disease progression.

The co-primary endpoints were:

PFS as determined by the investigator using RECIST v1.1 in the ITT-WT population
OS in the ITT-WT population
IMpower130 met its co-primary endpoints of OS and PFS.

A summary of the results is included below:

Safety for the Tecentriq and chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination. Grade 3 – 4 treatment-related adverse events (AEs) were reported in 73.2% of people receiving Tecentriq plus chemotherapy compared to 60.3% of people receiving chemotherapy alone. The most common Grade 3 – 4 AEs in people receiving Tecentriq plus chemotherapy were: an abnormal low count of a certain type of white blood cell (neutropenia, 32.1%), a decrease in red blood cells (anaemia, 29.2%), and a decreased neutrophil count (12.1%).

About NSCLC
Lung cancer is the leading cause of cancer death globally.[2] Each year 1.76 million people die as a result of the disease; this translates into more than 4,800 deaths worldwide every day.[2] Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.[3] NSCLC comprises non-squamous and squamous-cell lung cancer, the squamous form of which is characterised by flat cells covering the airway surface when viewed under a microscope.[3]

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

Currently, Roche has eight Phase III lung cancer studies evaluating Tecentriq alone or in combination with other medicines.

Tecentriq is already approved in the European Union, United States and more than 70 countries for people with previously treated metastatic NSCLC and for certain types of untreated or previously treated metastatic urothelial carcinoma (mUC).

On October 22, 2018 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported that new data from the company’s recently completed Phase 1b study with INO-5150 demonstrated a slowing of Prostate-Specific Antigen Doubling Time (PSADT) in men with prostate cancer (Press release, Inovio, OCT 22, 2018, View Source;PSA-Doubling-Time-Improvements-in-Prostate-Cancer-Patients-Treated-with-INO-5150/default.aspx [SID1234530272]). Eighty six percent (86%) of patients remained progression-free at Week 72 of the study. These data were presented in a poster entitled "Synthetic DNA immunotherapy in Biochemically Relapsed Prostate Cancer" at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 congress in Munich today.

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In this study, Inovio evaluated the tolerability and immunogenicity of INO-5150, a DNA vaccine encoding PSA and PSMA, with or without INO-9012 (encoding IL-12 immune adjuvant), in men with biochemically relapsed prostate cancer. The study demonstrated a slowing of PSA doubling time, a measure of disease progression, in a majority of patients on the study. In addition, 86% of patients were progression-free at Week 72 of the study, which in this treatment-refractory, high-risk patient population, is thought to be clinically promising. Importantly, analyses demonstrated that immunogenicity was observed in 77% (47/61) of patients by multiple immunologic assessments.

Previous results from the Phase 1b study were presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting and demonstrated that of the 61 evaluable patients, 77% (47/61) demonstrated T cell immunogenicity, and 38% (19/50) exhibited CD38+, Perforin+CD8+ T cell responses. Results presented at ASCO (Free ASCO Whitepaper) provided clinical data through week 72 and immunology data through week 27. The latest results being presented at ESMO (Free ESMO Whitepaper) update these data and report that 80% of evaluable patients in the trial demonstrated either INO-5150 specific T cell or antibody reactivity.

Dr. J. Joseph Kim, Inovio’s President and Chief Executive Officer, said, "The follow-up data and opportunity to showcase INO-5150 from our Phase 1 prostate cancer study further helps Inovio’s efforts to enter into a strategic development partnership to expand into a Phase 2 study. These follow-up results support the rationale for further development and provides the basis for a novel checkpoint combination cancer trial."

This patented approach of INO-5150 in combination with CELLECTRA delivery device is designed to help the body’s immune system overcome its "self-tolerance" to prostate cancer cells and mount a strong targeted CD8+ killer T cell response to eliminate the cancerous cells displaying these antigens. Moreover, PSMA is also one of 3 antigens comprising INO-5401, which is being tested in two separate Phase 1/2 trials as an immunotherapy to treat glioblastoma and metastatic bladder cancer in combination with Regeneron and Genentech/Roche’s checkpoint inhibitors, respectively.

About Prostate Cancer and Biochemically Recurrent Prostate Cancer (BRPC)

Prostate cancer is the second most frequently diagnosed cancer in men. Nearly three-quarters of the registered cases occur in developed countries. Accounting for nearly 300,000 deaths each year, prostate cancer is the sixth leading cause of death from cancer in men. There are about 60,000 patients each year in the US that develop biochemically recurrent prostate cancer (BRPC). The development of a new treatment for prostate cancer would be a significant medical advance given that current standard-of-care treatment options (surgery, radiation and hormone deprivation), while somewhat effective, all carry deleterious side effects and are often not a long-term cure.

On October 22, 2018 NuCana plc (NASDAQ: NCNA), a clinical-stage biopharmaceutical company focused on significantly improving treatment outcomes for patients with cancer, reported combined results from cohorts one and two of the ABC-08 Study at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2018 in Munich, Germany (Press release, Nucana BioPharmaceuticals, OCT 22, 2018, View Source [SID1234530269]). In this Phase Ib multi-center, open-label study in front-line treatment of patients with advanced biliary tract cancer, Acelarin combined with cisplatin was observed to continue to achieve approximately a doubling of the response rate expected with the standard of care, gemcitabine plus cisplatin. In addition, results showed the combination was well-tolerated and several patients achieved significant reductions in their tumor volume as well as further tumor shrinkage over time.

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Fourteen patients with advanced/metastatic biliary tract cancer received Acelarin (625mg/m2 or 725mg/m2) and cisplatin (25mg/m2) on days one and eight of a three-week cycle. In the intent-to-treat group of patients, a Complete Radiological Response was achieved in one patient and a Partial Response in six patients, resulting in an Objective Response Rate of 50%. In the eleven Efficacy Evaluable patients (defined as those patients who received at least one cycle of therapy), an Objective Response Rate of 64% was achieved.

"Building upon the interim analysis presented in January 2018 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, these data continue to be encouraging and suggest that the combination of Acelarin and cisplatin may represent an important advance in the standard of care treatment of advanced biliary tract cancer, a devastating disease for which there are no approved medicines," remarked Professor Juan Valle, Co-Chief Investigator of the ABC-08 Study and Professor and Honorary Consultant in Medical Oncology at the University of Manchester and The Christie NHS Foundation Trust, Manchester, United Kingdom.

Dr. Mairéad McNamara, Co-Chief Investigator of the ABC-08 Study and Senior Lecturer and Honorary Consultant in Medical Oncology at the University of Manchester and The Christie NHS Foundation Trust, added, "In addition to the encouraging response rate observed, which is approximately double that of the standard of care, I believe the ability of this combination to continue to shrink the tumor volume over time is also noteworthy. Some patients showed sustained and durable tumor shrinkage, which is not typically seen in this setting."

Additionally, the combination of Acelarin and cisplatin was well-tolerated over multiple cycles with no unexpected adverse events, no dose-limiting toxicities, no discontinuations due to Acelarin-associated toxicity and no Grade 4 adverse events.

Based on these data from the ABC-08 study and discussions with the U.S. Food and Drug Administration (FDA), NuCana anticipates initiating a global randomized Phase III clinical study comparing Acelarin (625mg/m2) and cisplatin (25mg/m2) with gemcitabine (1,000mg/m2) and cisplatin (25mg/m2) in patients with front-line advanced biliary tract cancer.

Hugh Griffith, NuCana’s Chief Executive Officer, said: "We are excited by the results achieved in this study. We have also been encouraged by the ongoing constructive dialogue with the FDA and look forward to initiating a front-line Phase III study of Acelarin plus cisplatin in patients with advanced biliary tract cancer."

A comparison of these data from the ABC-08 Study and the earlier ABC-02 Study, that established the current standard of care, is provided in the table below:

Objective Response Rates in ABC-08 and ABC-02

ABC-08 Study

ABC-02 Study*

NUC-1031 + cisplatin

625 mg/m2 or 725 mg/m2 + 25 mg/m2

gemcitabine + cisplatin

000 mg/m2 + 25 mg/m2

Complete Response

7% (1/14)

0.6% (1/161)

Partial Response

43% (6/14)

25.5% (41/161)

Objective Response Rate

50% (7/14)

26.1% (42/161)

*Valle et al. N Eng J Med 2010; 363:1273-1281

On October 22, 2018 Celgene Corporation (NASDAQ:CELG) reported the appointment of Dr. Alise Reicin to President, Global Clinical Development, reporting to Mark J. Alles, Chairman and Chief Executive Officer, effective November 1, 2018 (Press release, Celgene, OCT 22, 2018, View Source [SID1234530266]). In this role, Dr. Reicin will be responsible for all aspects of mid- to late-stage clinical development across Celgene’s portfolio and will serve on the company’s Executive Committee.

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"Dr. Reicin is an accomplished physician with an excellent record of developing important therapeutics for multiple cancer and inflammatory indications," said Mark J. Alles, Chairman and CEO of Celgene Corporation. "Led by Alise, our clinical development organization will be structured to more completely align with our strategy and mission to discover, develop and commercialize innovative therapies for patients with unmet need. She joins Dr. Rupert Vessey, President, Research & Early Development, and Dr. Jay Backstrom, Chief Medical Officer, as we deliver the potential of our deep and broad pipeline."

The appointment of Dr. Reicin is part of a deliberate strategy to strengthen Celgene for long-term success. This organizational change further establishes clinical development as another center of excellence and enhances strategic leadership in discovery, development and commercialization. Dr. Rupert Vessey continues to lead early research and development. Dr. Reicin will lead mid- to late-stage clinical development, clinical operations, biostatistics, project leadership and project management. Dr. Jay Backstrom maintains responsibility for our global regulatory strategy, drug safety, regulatory operations and pharmacovigilance. Nadim Ahmed and Terrie Curran continue to lead our global commercial and medical affairs organizations for the Hematology & Oncology and Inflammation & Immunology franchises, respectively.

Dr. Reicin was most recently Senior Vice President and Head of Global Clinical Development in Research and Development (R&D) at EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany. In this role, she has been responsible for the clinical development of assets across oncology and inflammatory indications, including anti-PD-L1 avelumab in solid tumors and cladribine in relapsing multiple sclerosis. Since joining EMD Serono in 2015, she has led clinical development, biostatistics, clinical operations, and the Japan and China R&D hubs. Prior to joining EMD Serono, Dr. Reicin served as Vice President, Project and Pipeline Leadership, Oncology Franchise at Merck, Sharp & Dohme (Merck). She led Merck’s immuno-oncology program and oversaw initial development and filing activities worldwide, including the first approval for pembrolizumab (KEYTRUDA) in the United States. Before joining Merck, Dr. Reicin was a faculty member at Columbia Medical School, and a physician and researcher at Columbia Presbyterian Hospital. She has a degree in biochemistry from Barnard College of Columbia University. She received her Medical Degree from Harvard Medical School, where she was enrolled in the Health Sciences and Technology program with MIT (Massachusetts Institute of Technology).